Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells

iScience

Michael P. Vincent¹  Evan Alexander Scott¹  Simseok A. Yuk²  Sijia Yi²  Sharan Bobbala²  Sun-Young Kim²  Fanfan Du² 

[1] SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, Republic of Korea;Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA;

关键词: Health sciences;    Drug delivery system;    Biological sciences;    Immunology;    Biotechnology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Plasmid DNA (pDNA) transfection is advantageous for gene therapies requiring larger genetic elements, including “all-in-one” CRISPR/Cas9 plasmids, but is limited by toxicity as well as poor intracellular release and transfection efficiency in immune cell populations. Here, we developed a synthetic non-viral gene delivery platform composed of poly(ethylene glycol)-b-poly(propylene sulfide) copolymers linked to a cationic dendritic peptide (DP) via a reduceable bond, PEG-b-PPS-ss-DP (PPDP). A library of self-assembling PPDP polymers was synthesized and screened to identify optimal constructs capable of transfecting macrophages with small (pCMV-DsRed, 4.6 kb) and large (pL-CRISPR.EFS.tRFP, 11.7 kb) plasmids. The optimized PPDP construct transfected macrophages, fibroblasts, dendritic cells, and T cells more efficiently and with less toxicity than a commercial Lipo2K reagent, regardless of pDNA size and under standard culture conditions in the presence of serum. The PPDP technology described herein is a stimuli-responsive polymeric nanovector that can be leveraged to meet diverse challenges in gene delivery.

【 授权许可】

Unknown